We plan to study the factors promoting progressive cartilage destruction in animal models of osteoarthrosis (Degenerative Joint Disease) to understand its pathophysiology in order to work toward its prevention. Since the pathology of osteoarthrosis involves destruction of the articular cartilage and the remodeling of the bone adjacent to the joints, we must use in vivo preparations. Because osteoarthrosis mainly affects older individuals and its development involves an interrelationship between a variety of tissues, organ cultures utilizing fetal materials are inappropriate. The effectiveness and reliance of our animal models has been established. The joint tissues are studied biochemically, metabolically and biomechanically. Having identified the initial tissue changes in osteoarthrosis we are now completing our study of the inter-relationships of the changes in bone, cartilage, and synovium to determine what makes joint deterioration progressive. We wish to continue our experiments designed to prevent mechanically induced joint deterioration from becoming progressive. We will use inter-related computer models and experimental models. In the process we are working to identify the threshold insults that provoke osteoarthrosis. Experimentally we will use both mechanical and antimetabolic means to prevent and suppress the critical steps in the development of osteoarthrosis from occurring.